Microbiome Metabolites and Alcohol in HIV to Reduce CVD RCT

NCT ID: NCT05288790

Last Updated: 2025-06-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-18
• Study Completion Date: 2027-02-28

Brief Summary

Among people living with HIV, heavy drinking increases the risk of heart disease and death. Studies suggest that alcohol changes the number and kind of bacteria in your gut and these changes increase the risk of heart disease and death. This randomized controlled trial will determine whether a pill containing healthy gut bacteria can increase the number good bacteria in the gut, lower levels of inflammation, and lower the risk of heart disease and death.

Detailed Description

Among people living with HIV (PLWH), heavy drinking increases the risk of cardiovascular disease (CVD) and death. Data suggest that alcohol-associated gut dysbiosis partially drives this risk. Whether interventions targeting alcohol-associated gut dysbiosis among PLWH improve dysbiosis, lower levels of microbial translocation, inflammation, and harmful metabolites (e.g., trimethylamine N-oxide [TMAO)]) is unknown. The investigators' hypothesis for this P01 application is that among PLWH, a probiotic can mitigate or reduce alcohol associated gut dysbiosis and lower levels of microbial translocation, inflammation, and improve metabolite profiles (Project 1); and that harmful levels of these metabolites will be associated with higher CVD and death risk (Project 2). This team, with expertise in alcohol, HIV, gut microbiome, and biomarker research has conducted two NIAAA funded trials, a metabolite study, and a gut microbiome study among Russian PLWH who are heavy drinkers. Data from these studies show that among PLWH: (1) heavy drinking is associated with incident CVD, death and gut dysbiosis (characterized by a reduction in butyrate producing bacteria); and (2) this gut dysbiosis is associated with inflammation, altered bile acids, and high TMAO levels. Given these data and reports from pilot studies showing that probiotics are safe, may improve gut dysbiosis and reduce inflammation among PLWH, the investigators propose an RCT among 250 PLWH with heavy alcohol consumption who are on antiretroviral therapy and have CD4+ counts≥350 cells/mm3 to compare the effects of a probiotic tailored to alcohol associated gut dysbiosis vs. placebo to: (1) improve GI dysbiosis; (2) reduce plasma metabolite (e.g., TMAO) and biomarker levels of microbial translocation and inflammation; and (3) lower CVD and mortality risk. All participants will receive evidenced-based counseling for alcohol use. The specific aims will compare the effects of a tailored probiotic vs. placebo at 6 months on (Aim 1) dysbiosis (fecal Firmicutes to Bacteroidetes (F/B) ratio, primary study outcome; fecal Lachnospiraceae-family of butyrate producers) and plasma metabolites (plasma butyrate, deoxycholic acid:cholic acid ratio, and TMAO) (Aim 2) biomarkers of inflammation plasma, IL-6, D-dimer, sCD14), microbial translocation [Lipopolysaccharide binding protein], (Aim 3) cardiovascular risk (Reynolds risk score), mortality risk (VACS index); (Aim 4 exploratory) alcohol consumption (% heavy drinking days in past month) and HIV disease progression (CD4 cell count). The investigators hypothesize that as compared with placebo, the probiotic arm will have significantly: (1) higher F/B ratio and levels of fecal Lachnospiraceae, plasma butyrate, deoxycholic acid: cholic acid ratio and lower levels of TMAO; (2) lower plasma biomarker levels of microbial translocation and inflammation; (3) lower Reynolds risk score and VACS index; (4) lower % heavy drinking days in the past month and higher CD4 cell counts. The findings from this RCT, Microbiome, mETabolites, and Alcohol in HIV to reduce CVD (META HIV CVD RCT), will inform probiotics' role as standard adjunctive therapy complementing alcohol interventions among PLWH who are heavy drinkers.

Conditions

Microtia; Dysbiosis; Alcohol Drinking; HIV Infections; Cardiovascular Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Study Supplement

Probiotic

Group Type: EXPERIMENTAL

Probiotic

Intervention Type: DIETARY_SUPPLEMENT

Dietary supplement

Study placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Placebo sachet

Interventions

Probiotic

Dietary supplement

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Placebo sachet

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• HIV infected

Exclusion Criteria

• Not fluent in English

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Louisville

OTHER

Sponsor Role: collaborator

Boston University

OTHER

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Matthew S.Freiberg

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Grace Wallace, BS

Role: CONTACT

grace.wallace@vumc.org

615-936-5356

Emily Smith, MPH

Role: CONTACT

emily.k.smith@vumc.org

6158757253

Facility Contacts

David Crenshaw, MSW

Role: primary

615-322-7343

Other Identifiers

P01AA029542

Identifier Type: NIH

Identifier Source: org_study_id

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